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AIM: To investigate the effect and possible mechanism of sakuranetin(SK)on 2,4,6-trinitroben-zenesulfonic acid (TNBS) -induced Crohn disease (CD) -like colitis in mice. METHODS: A total of 24 C57BL/6J mice were randomly divided into a control, model (TNBS), and SK (20 mg-kg'-d"1) treatment groups(TNBS+SK), with eight mice in each group. Colitis symptoms were evaluated using the disease activity index(DA1) and body weight change. The colon injury was evaluated based on colon length, histological inflammation score, and levels of intestinal mucosal inflammatory mediators(TNF-ot, IL-6, 1L-17A, and IL-1 p). The intestinal barrier function was assessed by measuring the levels of fluorescein isothiocyanate-dextran 4 kD(FD4)and intestinal fatty acid binding protein (1-FABP)in the peripheral blood, colonic transcpitliclial electric resistance (TEER), and intestinal bacterial translocation rate. (tCiic Ontology ((;O)and Kyoto Encyclopedia of Genes and Genomes(KEG(;) cnrichmciit analyses were performed to predict the potential pathways and SK mechanisms, followed by validation through animal experiments. RESULTS: The DAI score and body weight loss in the l -BS+SK group were significantly lower than those in the group hut higher than those in the control group (P<0. 05). The TMJS+SK group showed a significant reduction in colonic shortening, histological iiiflammatory scores, and levels of colonic mucosal inflammatoiy mediators compared to the TABS group, hut higher than those in the control group (P<0. 05). The levels of FD4 and 1-1ABP in the peripheral blood of the TMiS+SK group were significantly lower than those of the TJSBS group, hut higher than those of the control group(P

Objective　To investigate the effect of 7‑ketocholesterol (7‑KC) on apoptosis and to elucidate its underlying mechanism in pancreatic β‑cells. Methods　INS‑1 cells were treated with 0, 0.25, 2.5 and 25 μmol/L 7‑KC for 24 h, and the concentration inducing apoptosis of INS‑1 cells was detected by western blotting. Furthermore, the cells were divided into four groups: blank group, 25 μmol/L 7‑KC treatment group, 7‑KC treatment and pretreated with 1 mmol/L endoplasmic reticulum (ER) stress inhibitor 4‑phenylbutyric acid (4‑PBA) group, and 1 mmol/L 4‑PBA group. The expression of ER stress marker proteins [inosital‑requiring enzyme‑1α (IRE‑1α), protein kinase R‑like endoplasmic reticulum kinase (PERK), activating transcription factor 4 (ATF4), phosphorylated α subunit of eukaryotic initiation factor 2 (p‑eIF‑2α), α subunit of eukaryotic initiation factor 2 (eIF‑2α), C/Ebp‑homologous protein (CHOP), phosphorylated inosital‑requiring enzyme‑1 (p‑IRE‑1α), phosphorylated protein kinase R‑like endoplasmic reticulum kinase (p‑PERK), activating transcription factor 6α (ATF‑6α)], apoptosis proteins [B‑cell lymphoma‑2 (Bcl‑2), Bcl2‑associated X (Bax), cleaved cysteinyl aspartate‑specific proteinase‑3 (cleaved‑Caspase 3)], ER morphology and interaction proteins of ER [glucose regulated protein 78 (GRP78)] were elucidated via western blotting, flow cytometry and immunofluorescence, transmission electron microscopy and co‑immunoprecipitation, in order to verify the role of ER stress in β‑cell function impairment by 7‑KC. Two‑tailed Student′s t tests were performed to compare means between two groups. ANOVA followed by Bonferroni′s multiple comparisons was used to compare means from three or more groups. Results　The cleaved‑Caspase3 was increased dose‑dependently and upregulated obviously at 25 μmol/L 7‑KC treatment group (P<0.01). Meanwhile, the dilation and vesiculation of ER, and ER stress‑sensing proteins p‑PERK, p‑IRE‑1α, ATF6, p‑eIF‑1, ATF4, and CHOP were dramatically upregulated at 25 μmol/L 7‑KC treatment group. Compared with 25 μmol/L 7‑KC treatment group, the further study showed that ER stress protein expressions were downregulated, and apoptosis proteins expressions were decreased at 25 μmol/L 7‑KC treatment and pretreated with 1 mmo/L 4‑PBA group (P<0.05). Co‑immunoprecipitation demonstrated that the binding of molecular chaperones GRP78 and PERK was inhibited at 25 μmol/L 7‑KC treatment group, and furthermore increased PERK autophosphorylation and then activated ER stress. Conclusion　7‑KC activates ER stress and promotes apoptosis by inhibiting the GRP78‑PERK interaction in pancreatic β cells. [ABSTRACT FROM AUTHOR]